This invention relates to novel bis-triazole derivatives which have antifungal activity and are useful in the treatment of fungal infections in animals, including humans, and as agricultural fungicides.
British patent application No. 2,078,719A, published Jan. 13, 1982 and European patent application No. 44,605, published Jan. 27, 1982 (both assigned to Imperial Chemical Industries Limited) disclose compounds of the general formula: ##STR2## where R.sup.1 is an optionally-substituted alkyl, cycloalkyl (e.g., cyclopentyl or cyclohexyl), aryl (e.g., phenyl or 2,4-dichlorophenyl) or aralkyl (e.g., benzyl) group, and Y.sup.1 and Y.sup.2 are .dbd.CH or .dbd.N--; and salts or metal complexes and ethers or esters thereof. These compounds are stated to be useful as fungicides as plant growth regulants. They are also stated to be active against the fungus diseases of humans. Among the compounds specifically disclosed therein are such bis-triazole derivatives as 2-(2,4-dichlorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol and its corresponding 2- and 4-chlorophenyl analogs. The corresponding 3-chlorophenyl and 4-bromophenyl compounds are also embraced by the statement of invention. However, these particular compounds have now been found to be teratogenic, which severely limits their use in treating human mycoses.
U.S. Pat. No. 4,404,216, issued Sept. 13, 1983 is directed to the single antifungal compound 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol, a compound having the above formula but wherein R.sup.1 is 2,4-difluorophenyl.
Since the 1960's an increase in fungal infections, particularly those caused by Candida and Aspergillus species, has been reported among immunocompromised patients. While any Aspergillus species can be the responsible cause of aspergillosis, A. fumigatus is the most prevalent cause, followed closely by A. flavus. The availability of agents effective against such opportunistic pathogens is, therefore, highly desirable.